The sensitivity of an ion analytical instrument, such as a mass spectrometer, depends in part upon the efficiency with which the coupled ion source generates ions from the analytical sample and then delivers those ions to the instrument for analysis.
Efficiency of delivery can be compromised by fragmentation, or decay, of molecular ions prior to analysis. In-source and post-source ion decay is of particular relevance in laser desorption ionization sources, due to the high energies imparted by the laser pulse, and in orthogonal extraction geometries, which require that ions survive at least 2–3 msec before analysis.
One solution to ion fragmentation is to effect collisional cooling of ions before analysis.
Collisional cooling in the first quadrupole ion guide of an orthogonal extraction QqTOF mass spectrometer has been described, both with an electrospray ion source and a laser desorption ionization (LDI) source. See, e.g., WO 99/30351 and Loboda et al., Rapid Communic. Mass Spectrom. 14:1047–1057 (2000).
Collisional cooling earlier in the ion trajectory, within the ion source itself, has also been described.
WO 00/77822, for example, describes a matrix-assisted laser desorption ionization (MALDI) source having a static pressure in the range of 0.1 to 10 torr; the rapid in-source collisional cooling is said to improve the stability of the produced ions. EP 0964427 describes a static ambient pressure MALDI apparatus.
U.S. Pat. No. 6,515,280 (Baykut) describes a MALDI source in which a gas pulse is introduced exactly at the point of laser desorption in synchrony with the laser pulse; the transient pressure increase is said to effect immediate in-source collisional cooling. U.S. patent application Ser. No. 2003/0098413 (Weinberger et al.) describes a laser desorption ionization source in which cooling gas is introduced at the laser-interrogated surface of the LDI probe. In contrast to the device of Baykut, in which the gas introduced at the laser desorption probe surface is in free communication with a subsequent multipole ion guide, the laser desorption probe in Weinberger et al. is communicably segregated from the first multipole ion guide of the analytical instrument.
Although collisional cooling is reported to improve ion stability in each of these various devices, the gas flow fields are nonoptimal through most parts of these devices, compromising the collection, collimation and output of ions.
In the high pressure MALDI sources, for example, gas resting statically in front of the sample, with no means present for facilitating momentum transfer, can lead to ion loss. In devices in which gas is dynamically introduced at the probe surface, gas introduction is effected through asymmetrically arranged channels, giving rise to asymmetrical collisional forces. And in devices in which ions are injected essentially immediately into RF multipoles, with collisional cooling to be effected within the multipole, most ions are exposed to very high electric field strengths, giving rise to additional initial heating.
Thus, there is a need in the art for ion sources, particularly laser desorption ionization sources, that both effect rapid collisional cooling and in which the gas flow fields are configured throughout the device to optimize ion delivery to an ion analytical instrument to which the source is operably coupled.